The anemias associated with renal disease are important symptoms associated with this disease which ranks fourth in our country as the cause of death. It has been suggested that alterations in tissue levels of cyclic AMP and/or cyclic GMP in various tissues lead to regulation of certain biologic processes including erythrocyte production. The erythropoietic effects of lactate will be evaluated in marrow culture systems. The effects of erythropoietin on marrow cyclic GMP levels and correlations between proliferative or differentiative actions and cyclic GMP will be attempted. The possible cholinergic link between cyclic GMP and the release of renal lysosomal enzymes into the plasma will be studied . Abnormal renal endocrine function will be compared with alterations in renal cyclic nucleotides. A model test animal being used in this laboratory is the New Zealand Black mouse. These animals develop a spontaneous renal disease with an associated anemia and will be used to evaluate alterations in renal cyclic AMP with renal endocrine dysfunction.